On June 28, 2022 Domain Therapeutics, a biopharmaceutical company focusing on the research and development of innovative drugs targeting G Protein-Coupled Receptors (GPCRs) in immuno-oncology (IO), reported that it obtained a single digit multimillion milestone payment from Merck as part of the €240m ($261m) milestone payments and undisclosed royalties collaboration and license partnership signed in 2017 (Press release, Domain Therapeutics, JUN 28, 2022, View Source [SID1234616336]).
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M1069 is an orally available small molecule antagonist of adenosine receptors discovered jointly by both companies. This productive and successful partnership, based on Domain’s expertise in GPCR medicinal chemistry, pharmacology and drug discovery, led to the identification of the drug candidate M1069 to be included in the oncology pipeline of Merck.
Over the last years, several GPCRs were identified as targets to address tumor immunosuppressive strategies to evade immune responses, even in case of immune-checkpoint inhibitor treatment. M1069 aims at thwarting one of these immunosuppressive strategies whereby adenosine is released in the tumor microenvironment.
In the meantime, the Company has built a unique and well-differentiated pipeline with diverse programs targeting specific immunosuppression mechanisms, aiming to provide therapeutic solutions to patients unresponsive to immune-checkpoint inhibitors. This outstanding ability to deliver candidates against validated GPCR targets, as well as to innovate with first-in-class programs focusing on brand new GPCR targets in immuno-oncology, has put Domain at the forefront of innovation in the field.
"This milestone is a great recognition of the ability of our research teams and of the Company to deliver cutting edge candidates able to reach the clinical development stage," says Dr. Stephan Schann, Vice-President of Research and Partnerships at Domain Therapeutics. "Merck is a valuable and respectful partner and our fruitful collaboration has confirmed Domain’s position as a key player in immuno-oncology R&D."
"We were extremely pleased to see M1069 entering the clinical stage earlier in 2022. Reaching first-in-human & single ascending dose phase 1 constitutes a significant step towards the delivery of a novel drug for the treatment of cancer patients", said Dr. Asmaa Boudribila, Medical Director at Domain Therapeutics. "I look forward to following the next stages of clinical development and to the future successes of this promising product."
"Following the launching in the clinic of M1069 by Merck, Domain is very proud to prepare the entrance into the clinic, at the end of 2022, of its first fully proprietary product, the EP4R antagonist candidate DT-9081. The upcoming entry into the clinical of a candidate targeting a distinct immunosuppressive mode of action will further confirm our position as a leader in GPCR targeting-therapeutics in immuno-oncology," added Pascal Neuville, CEO of Domain Therapeutics. "In the coming years, Domain aims to deliver a series of well-positioned candidates for a personalized medicine approach for patients.
This Phase 1 study is conducted in three cancer centers: New York (US), Nashville (US) and Toronto (CAN).
About Adenosine receptors
Adenosine is a powerful immunosuppressive substance produced inside tumors as a result of stress such as hypoxia. Adenosine can act directly on tumor cells to promote their growth, survival and dissemination. In some cases, it is responsible for resistance to certain anti-tumor interventions, such as chemotherapy and radiation. The adenosine receptors, expressed on the surface of immune cells, mediate the immunosuppressive effects of adenosine. The adenosine-driven impairment of tumor-infiltrating lymphocytes (mainly CD8+ T cells and NK cells) and myeloid cells (dendritic cells, macrophages), mediated by adenosine receptors, requires the development of specific inhibitors. For the last few years, the pharma industry has been investigating the benefit of combining adenosine receptor antagonists with immune checkpoint inhibitors (ICI) in order to decrease adenosine-mediated resistance and restore ICI antitumor activity.